Abstract

Little is known about responses of intestinal L-cells to chemical or cytokine-mediated attack and how these compare with pancreatic β- or α-cells. Administration of streptozotocin to mice induced severe diabetes, islet lymphocytic infiltration, increased α-cell proliferation and decreased numbers of β- and L-cells. In vitro, streptozotocin and cytokines reduced cell viability with higher lethal dose 50 values for α-TC1 cells. mRNA expression of Glut2 was lower and Cat was greater in GLUTag and α-TC1 cells compared with MIN6 cells. Cytotoxins affected the transcription of genes involved in secretion in GLUTag and MIN6 cells. They are also involved in upregulation of antioxidant defence enzymes, transcription of NfκB and Nos2, and production of nitrite in all cell types. Cytotoxin-induced DNA damage and apoptosis were apparent in all cells, but α-TC1 cells were less severely affected. Thus, responses of GLP1-secreting L-cells to cytotoxicity resemble β-cells, whereas α-cells are resistant due to differences in the expression of genes involved in cytotoxicity or antioxidant defence.